1. Resynchronization/defibrillation for
Ambulatory Heart Failure Trial
RAFT
A Multicentre Randomized Double Blinded
Controlled Trial
Anthony S.L. Tang MD, George A. Wells PhD, Mario Talajic
MD, Malcolm O. Arnold MD, Robert Sheldon MD, Stuart
Connolly MD, Stefan Hohnloser MD, Graham Nichol MD,
David Birnie MD, John L. Sapp MD, Raymond Yee MD,
Jeffrey S. Healey MD, Jean L. Rouleau for the RAFT
investigators
AHA Late Breaking Clinical Trial
November 14 2010
Chicago

2. Disclosure
RAFT is a peer-reviewed funded project by the Canadian
Institutes of Health Research through a University-
Industry program
• CIHR provided financial support
• Medtronic of Canada provided financial and in-kind support
Anthony Tang Disclosure Information
Stock or stock option in any device company: None
Research Support: Medtronic, St. Jude Medical, Boston
Scientific
Speaker Bureau: None

3. Hypothesis and Endpoints
Primary Hypothesis
The addition of CRT to ICD and optimized medical therapy will
reduce the primary outcome of total mortality or
hospitalizations for heart failure in patients with mild to
moderate heart failure symptoms, and wide QRS.
Outcome Measures
Primary – composite of death from any cause or
hospitalization for heart failure
Secondary – death from any cause, death from
cardiovascular cause, hospitalization for heart failure
Hospitalization for heart failure is defined as an admission to a health-care facility for > 24
hours with worsening heart failure. Hospitalizations > 24 hours were adjudicated by an
event committee unaware of the patient treatment allocation

4. Study Design
• Parallel, randomized control trial
• Eligible patients were randomly assigned in a 1:1 ratio to receive
• an ICD
• an ICD with CRT
• Stratified by center, atrial rhythm (permanent atrial fibrillation or flutter,
or sinus or atrial pacing), and a planned implantation of a single- or dual-
chamber ICD
• Double-Blinding
• The patients and the general health care providers including the team that
was responsible for heart failure management and reporting of clinical
events were unaware of treatment allocation
• The arrhythmia team were aware of treatment allocation
• Patients assessment and follow-up
• At baseline
• 12-lead ECG, QOL assessment, 6-minute walk test, and medication were taken
• Follow-up at 1 month, then every 6 months
• 12-lead ECG, QOL assessment, 6-minute walk test , medication, and device
interrogation were done

5. Key Eligibility Criteria
• NYHA Class II and III (NYHA Class III not included after
Feb 2006)
• QRS duration 120 ms or Paced QRS 200 ms
• LVEF 30% by MUGA or LVEF 30% and LVEDD > 60mm
by echocardiogram within 6 months of randomization
• ICD indication: 1° or 2° prevention
• Optimal heart failure pharmacological therapy
• Normal sinus rhythm or chronic permanent atrial
fibrillation or flutter with a resting ventricular rate ≤ 60
bpm and ventricular rate ≤ 90 bpm during a 6 minute
walk test or intended to perform AV junction ablation

6. RAFT Centers
Canada 24 centres 1617 patients (90%)
Europe & Turkey 8 centres 137 patients (7.6%)
Australia 2 centres 44 patients (2.4%)

7. Results
Enrolled and
Consented
Randomized (N=1798)
Allocation
Allocated to ICD/CRT (N=894)
Allocated to ICD (N=904) Device Implanted (N=888)
Device Implanted (N=898) Device Not Implanted (N=6)
Device Not Implanted (N=5) 2 patient/physician refusal
4 patient/physician refusal 4 deaths (1 suicide) before implant
1 death before device implant LV lead successful implant (N=841, 95%)
Follow-up
Mean 40±20
months
Lost to follow-up (N=1) Lost to follow-up (N=2)
Cross-over Patient Withdrawal (N=4) Patient Withdrawal (N=8)
Cardiac Transplant (N=5) Cardiac Transplant (N=7) Cross-over
ICD to ICD/CRT
ICD/CRT to
36 (4.0%)
ICD
before
Analysis 47 (5.3%)
reaching 1°
failed LV lead
endpoint
Analyzed (N=904) Analyzed (N=894) implant
60 (6.6%) after
Excluded from analysis (N=0) Excluded from analysis (N=0) 6 (0.7%) non-
reaching 1°
functioning LV
endpoint
lead

8. Patient Characteristics at Baseline
Variables ICD ICD-CRT
(N=904) (N=894)
Age - yr 66.2±9.4 66.2±9.3
Male sex - no. (%) 732 (81.0) 758 (84.8)
Underlying Heart Disease - no. (%)
Ischemic heart disease 587 (64.9) 614 (68.7)
Nonischemic heart disease 317 (35.1) 280 (31.3)
NYHA class - no. (%)
Class II 730 (80.8) 708 (79.2)
Class III 174 (19.2) 186 (20.8)
LV Ejection Fraction - % 22.6±5.1 22.6±5.4
Atrial rhythm - no. (%)
Permanent atrial fibrillation or flutter 115 (12.7) 114 (12.8)
Sinus or atrial paced 789 (87.3) 780 (87.2)
Hypertension - no. (%) 397 (43.9) 402 (45.0)
Diabetes mellitus - no. (%) 313 (34.6) 293 (32.8)
Previous Percutaneous coronary intervention - no. (%) 208 (23.0) 220 (24.6)
Previous CABG - no. (%) 313 (34.6) 293 (32.8)
Current cigarette smoking - no. (%) 127 (14.0) 121 (13.5)
Peripheral vascular disease - no. (%) 90 (10.0) 88 (9.8)
Hospitalization for heart failure in the previous 6 months - no. (%) 223 (24.7) 238 (26.0)
Intrinsic QRS duration
No. of paients 837 826
Mean – msec. 158.3±24.0 157±23.6
Paced QRS duration
No. of patients 67 68
Mean - mesc 210.0±18.3 206.5±24.0
QRS morphologic type - no. (%)
Right bundle-branch block 93 (10.3) 68 (7.6)
Left bundle-branch block 643 (71.1) 652 (72.9)
NIVCD 101 (11.2) 106 (11.9)
Ventricular paced 67 (7.4) 68 (7.6)

9. Patient Characteristics at Baseline
Variables ICD ICD-CRT
(N=904) (N=894)
Medications - no. (%)
Beta-blocker 805 (89.0) 808 (90.4)
ACE inhibitor or ARB 878 (97.1) 859 (96.1)
Spironolactone 378 (41.8) 372 (41.6)
Digoxin 319 (35.3) 301 (33.7)
Aspirin 622 (68.8) 584 (65.3)
Warfarin 298 (33.0) 310 (34.7)
Clopidogrel 145 (16.0) 134 (15.0)
Statin 618 (68.4) 607 (67.9)
Diuretics 756 (83.6) 757 (84.7)
Calcium-Channel Blocker 83 (9.2) 101 (11.3)
Amiodarone 124 (13.7) 140 (15.7)
Other antiarrhythmia drug 8 (0.9) 12 (1.3)
6-minute walk test distance
No. of patients 765 789
Mean - m 354.9±110.1 351.3±106.7
Estimated glomerular filtration rate 60.8±21.9 59.5±19.8
No. of patients 897 885
Rate - ml/min/1.73 m2
<30 - no. (%) 63 (7.0) 57 (6.4)
30-59 - no. (%) 383 (42.7) 398 (45.0)
>60 -no. (%) 516 (50.3) 430 (48.6)

10. Kaplan-Meier Estimates of the
Primary Outcome
1 Death or Hospitalization for Heart Failure
0.8
ICD/CRT
(5-yr HF-free survival rate 0.576)
Event-free Survival
0.6
HR (95% CI) 0.75 (0.64, 0.87)
P=0.0002
0.4
ICD
(5-yr HF-free survival rate 0.487)
0.2
0
00 1
366 2
731 3
1096 4
1461 5
1827 6
2192
Years of Follow-up
No. at Risk
ICD/CRT 894 790 615 429 278 130 41
ICD 904 770 572 384 214 101 19

11. Kaplan-Meier Estimates of
All cause Mortality
1
Death at Any Time During the Study
ICD/CRT
0.8 (5-yr survival rate 0.714)
Event-free Survival
0.6
HR (95% CI) 0.75 (0.62, 0.91) ICD
P=0.003
0.4 (5-yr survival rate 0.654)
0.2
0
00 1
366 2
731 3
1096 4
1461 5
1827 6
Years of Follow-up
No. at Risk
ICD/CRT 894 849 685 502 333 167 53
ICD 904 841 670 482 289 149 35

12. Risk of Death or Hospitalization for
Heart Failure
Outcomes ICD only ICD/CRT Hazard Ratio P Value
(N=904) (N=984) (95% CI)
All patients
Primary outcome
Death or hospitalization for heart failure 364 (40.3) 297 (33.2) 0.75 (0.64-0.87) 0.0002
Secondary Outcomes
Death from any cause 236 (26.1) 186 (20.8) 0.75 (0.62-0.91) 0.003
Death from cardiovascular cause 162 (17.9) 130 (14.5) 0.76 (0.60-0.96) 0.019
Hospitalization for heart failure 236 (26.1) 174 (19.5) 0.68 (0.56-0.83) <0.0001
NYHA class II patients
No. of patients 730 708
Primary outcome
Death or HF hospitalization 253 (34.7) 193 (27.3) 0.73 (0.61-0.88) 0.001
Secondary Outcomes
Death from any cause 154 (21.1) 110 (15.5) 0.71 (0.56-0.91) 0.006
Death from cardiovascular cause 100 (13.7) 74 (10.5) 0.73 (0.54-0.99) 0.043
Hospitalization for heart failure 159 (21.8) 115 (16.2) 0.70 (0.55-0.89) 0.003
NYHA class III patients
No. of patients 174 186
Primary outcome
Death or hospitalization for heart failure 111 (63.8) 104 (55.9) 0.76 (0.58-0.99) 0.04
Secondary Outcomes
Death from any cause 82 (47.1) 76 (40.9) 0.79 (0.58-1.08) 0.135
Death from cardiovascular cause 62 (35.6) 56 (30.1) 0.77 (0.54-1.10) 0.154
Hospitalization for heart failure 77 (44.3) 59 (31.7) 0.63 (0.45-0.88) 0.006

13. Kaplan-Meier Estimates of
the Primary Outcome and Death by NYHA Class
NYHA Class II NYHA Class III
1
Death or Hospitalization for Heart Failure 1 Death or Hospitalization for Heart Failure
ICD/CRT 0.8
0.8
Event-free Survival
Event-free Survival
ICD/CRT
0.6 0.6
ICD
0.4 0.4
ICD
0.2
HR (95%CI) 0.73 (0.61, 0.88) 0.2
HR (95%CI) 0.76 (0.58, 0.99)
P=0.001 P=0.04
0 0
0
0 1
366 2
731 3
1096 4
1461 5
1827 6 00 1
366 2
731 3
1096 4
1461 5
1827 6
Years of Follow-up Years of Follow-up
No. at Risk No. at Risk
ICD/CRT 708 640 488 315 181 70 15 ICD/CRT 186 150 127 114 97 60 26
ICD 730 638 465 299 146 57 6 ICD 174 132 107 85 68 44 13
1 Death from any cause 1 Death from any cause
ICD/CRT
0.8 0.8
ICD/CRT
Event-free Survival
Event-free Survival
0.6 ICD 0.6
ICD
0.4 0.4
HR (95% CI) 0.71 (0.56, 0.91) HR (95% CI) 0.79 (0.58, 1.08)
0.2 0.2
P=0.006 P=0.135
0 0
0
0 1
366
2
731
3
1096
4
1461
5
1827
6 00 1
366 2
731 3
1096 4
1461 5
1827 6
Years of Follow-up Years of Follow-up
No. at Risk No. at Risk
ICD/CRT 708 679 530 361 206 89 20 ICD/CRT 186 170 155 141 127 78 33
ICD 730 687 533 366 189 83 13 ICD 174 154 137 116 100 66 22

14. Primary end point:
Sub-group Analysis

15. 30 Days Post Device Implantation
Adverse Events
Patients with Adverse Events within 30 Days of Device Implantation
Adverse Event ICD ICD-CRT p-value
(N=899) (N=888)
Hemo/pneumothorax 8 (0.89) 11 (1.24) 0.47
Pocket hematoma 11 (1.22) 14 (1.58) 0.53
Pocket infection 16 (1.78) 21 (2.36) 0.39
Tamponade 2 (0.22) 1 (0.23) 1
Lead dislodgement 20 (2.22) 61 (6.87) <0.001
Coronary sinus dissection 0 (0.0) 11 (1.24) <0.001
Device pocket revision 1 (0.11) 4 (0.45) 0.22

16. Conclusion
Among patients with NYHA class II or III heart failure
and left ventricular ejection ≤ 30%, and wide QRS,
the addition of CRT to ICD reduces
• death and hospitalization for heart failure
• All cause mortality
• with an absolute reduction of 6% over a treatment period
of 5 years
• 14 patients would need to be treated for 5 years to
prevent 1 death
• Hospitalization for heart failure
• 11 patients would need to be treated for 5 years to
prevent 1 hospitalization for heart failure

17. Back Up Slides

18. RAFT Team
• RAFT Coordinating Centre - U. of Ottawa Heart Institute
• RAFT Coordination Team - G. Wells, A. Tang, P. Theoret-
Patrick, M. Luce, L. Yetisir
• RAFT Executive Committee - A. Tang, G. Wells, M. Talajic,
M. Arnold, R. Sheldon, S. Connolly, S. Hohnloser, G. Nichol, J.
Rouleau
• DSMB Committee Chair - LB Mitchell
• Clinical Adjudication Committee Chair - A. Gillis
• Device Committee Co-chairs - L. Sterns, J. Sapp
• RAFT investigators and coordinators from 34 centres